Bladder-Sparing Options for BCG-Unresponsive Bladder Cancer

Wei Shen Tan, MD, PhD, and Ashish Kamat, MD, MBBS, MD Anderson Cancer Center, Houston, TX, discuss the options for a patient who develops disease recurrence following treatment with bacillus Calmette-Guerin therapy, and who is unwilling to undergo radical cystectomy.

Transcript:

Wei Shen Tan, MD:
I'm Shen Tan. I'm a Urology Fellow here at MD Anderson Cancer Center.

Ashish Kamat, MD:
I'm Ashish Kamat, Professor of Urologic Oncology at MD Anderson Cancer Center. It's a great pleasure to be joining you guys today to discuss our case.

Wei Shen Tan, MD:
The case that we're talking about today is treating high-grade recurrence in non-muscle invasive bladder cancer following BCG therapy. We're going to go through a case to illustrate an example on how we would manage this patient.

This patient is a 70-year-old male patient with a 40 cigarette pack-year history that presents with gross hematuria. He had an office cystoscopy, which suggests that a three-centimeter papillary-looking tumor on the posterior bladder wall. CT scan imaging did not suggest any upper tract lesions or any nodal or metastatic disease. His renal function was fine. He was then taken to the operating room for (transurethral resection of bladder tumor) TURBT, which suggested PT1 with carcinoma in situ with muscle in the specimen, which was absent for tumor.

How would you manage this patient typically, Dr Kamat?

Ashish Kamat, MD:
One of the things we think about when we see a patient that has had BCG therapy and then has a recurrence, is this recurrence dangerous or it's just one of the recurrences that occurs during the natural history of this patient?

Because of that, the thought process is, "Is this low grade or high grade?" That's the first question. The second is, "What is the stage of this tumor and how does it compare to the tumor that the patient initially presented with?" Then the third thing we always factor in is, "Has this patient received adequate BCG?" What do we mean by adequate BCG? Well, for the purposes of tumor biology and immunology, adequate BCG is induction and at least 1 maintenance course. Clearly with BCG, the ideal duration of treatment is 1 to 3 years, but for the initiation and the recruitment of the appropriate cells and the cytokine release, the Th1 and Th2 response, it's induction and 1 maintenance course, so we think of that.

Now in this particular case, the patient has a high-grade recurrence, so that's a checkbox in whether it's going to be dangerous or not for the patient. The initial diagnosis is T1 high grade. This patient essentially is considered high risk. We'll be considering recommending this patient to get adequate BCG, which would be induction and at least 1 maintenance course.

Wei Shen Tan, MD:
The patient then went on to induction BCG, which comprise typically 6 weekly installations, which he tolerated quite well. He had a 3-month cystoscopy, which was negative, but he had a biopsy at that 3-month cystoscopy, which actually suggested carcinoma in situ. So how would you proceed now at 3 months, now he's got carcinoma in situ, but no papillary tumor start to come up?

Ashish Kamat, MD:
This exactly fits in with what we were talking about earlier. Has this patient had a recurrence? Yes. Is it high grade? Yes. Has it progressed? No. Has the patient had adequate BCG? No. Because the patient has not had that induction and an additional maintenance course. For this patient, clearly an additional maintenance course of BCG is very appropriate and it's something we would recommend.

Wei Shen Tan, MD:
Okay. Would you go for an additional maintenance of 3 weekly, or would you re-challenge with maybe an additional induction course of 6 weekly typically for this patient?

Ashish Kamat, MD:
There is no data suggests that a repeat induction is any more effective than continuing on to maintenance therapy. For this particular patient, the recommendation essentially would be to do another course of maintenance. If you give another re-induction, it doesn't hurt, but it won't help.

Wei Shen Tan, MD:
Moving on. He then subsequently had his blood biopsy at 6 months, which did not suggest any evidence of any tumor. He proceeded on with maintenance BCG. Unfortunately, at 12 months, he did develop disease recurrence and histology would suggest high-grade Ta with CIS. How would you proceed now with this case, subsequently?

Ashish Kamat, MD:
Again, keeping all those parameters in mind, this patient had an initial response, has a recurrence, it's high grade, so that checks that box. This patient did get adequate BCG, that checks that box. But now has a recurrence and it hasn't progressed, but it's still a high-grade recurrence.

This patient falls into the category of being considered BCG-unresponsive. Currently, we have 2 approved drugs, pembrolizumab, which is approved and available based on the data from KEYNOTE-057, and nadofaragene, which is FDA approved, but not yet available. Of course, the de facto standard of care in the United States is a combination chemotherapy with gemcitabine and docetaxel.

Now these are all to be discussed with the patient, but we have to always remind the patient that the standard treatment based on all the guidelines is a radical cystectomy, which is removal of the bladder, as our listeners know. But we have to discuss the other options. Essentially, have an informed discussion with the patient and then see what the patient would like to do.

Wei Shen Tan, MD:
Great. That concludes our discussion of the case. Thank you very much.

Ashish Kamat, MD:
Thank you.